Neural Correlates of Vocal Production and Motor Control in Human Heschl's Gyrus.

The present study investigated how pitch frequency, a perceptually relevant aspect of periodicity in natural human vocalizations, is encoded in Heschl's gyrus (HG), and how this information may be used to influence vocal pitch motor control. We recorded local field potentials from multicontact depth electrodes implanted in HG of 14 neurosurgical epilepsy patients as they vocalized vowel sounds and received brief (200 ms) pitch perturbations at 100 Cents in their auditory feedback. Event-related band power responses to vocalizations showed sustained frequency following responses that tracked voice fundamental frequency (F0) and were significantly enhanced in posteromedial HG during speaking compared with when subjects listened to the playback of their own voice. In addition to frequency following responses, a transient response component within the high gamma frequency band (75-150 Hz) was identified. When this response followed the onset of vocalization, the magnitude of the response was the same for the speaking and playback conditions. In contrast, when this response followed a pitch shift, its magnitude was significantly enhanced during speaking compared with playback. We also observed that, in anterolateral HG, the power of high gamma responses to pitch shifts correlated with the magnitude of compensatory vocal responses. These findings demonstrate a functional parcellation of HG with neural activity that encodes pitch in natural human voice, distinguishes between self-generated and passively heard vocalizations, detects discrepancies between the intended and heard vocalization, and contains information about the resulting behavioral vocal compensations in response to auditory feedback pitch perturbations. SIGNIFICANCE STATEMENT: The present study is a significant contribution to our understanding of sensor-motor mechanisms of vocal production and motor control. The findings demonstrate distinct functional parcellation of core and noncore areas within human auditory cortex on Heschl's gyrus that process natural human vocalizations and pitch perturbations in the auditory feedback. In addition, our data provide evidence for distinct roles of high gamma neural oscillations and frequency following responses for processing periodicity in human vocalizations during vocal production and motor control.

Coding of repetitive transients by auditory cortex on posterolateral superior temporal gyrus in humans: an intracranial electrophysiology study.

Evidence regarding the functional subdivisions of human auditory cortex has been slow to converge on a definite model. In part, this reflects inadequacies of current understanding of how the cortex represents temporal information in acoustic signals. To address this, we investigated spatiotemporal properties of auditory responses in human posterolateral superior temporal (PLST) gyrus to acoustic click-train stimuli using intracranial recordings from neurosurgical patients. Subjects were patients undergoing chronic invasive monitoring for refractory epilepsy. The subjects listened passively to acoustic click-train stimuli of varying durations (160 or 1,000 ms) and rates (4-200 Hz), delivered diotically via insert earphones. Multicontact subdural grids placed over the perisylvian cortex recorded intracranial electrocorticographic responses from PLST and surrounding areas. Analyses focused on averaged evoked potentials (AEPs) and high gamma (70-150 Hz) event-related band power (ERBP). Responses to click trains featured prominent AEP waveforms and increases in ERBP. The magnitude of AEPs and ERBP typically increased with click rate. Superimposed on the AEPs were frequency-following responses (FFRs), most prominent at 50-Hz click rates but still detectable at stimulus rates up to 200 Hz. Loci with the largest high gamma responses on PLST were often different from those sites that exhibited the strongest FFRs. The data indicate that responses of non-core auditory cortex of PLST represent temporal stimulus features in multiple ways. These include an isomorphic representation of periodicity (as measured by the FFR), a representation based on increases in non-phase-locked activity (as measured by high gamma ERBP), and spatially distributed patterns of activity.

Intracranial study of speech-elicited activity on the human posterolateral superior temporal gyrus.

To clarify speech-elicited response patterns within auditory-responsive cortex of the posterolateral superior temporal (PLST) gyrus, time-frequency analyses of event-related band power in the high gamma frequency range (75-175 Hz) were performed on the electrocorticograms recorded from high-density subdural grid electrodes in 8 patients undergoing evaluation for medically intractable epilepsy. Stimuli were 6 stop consonant-vowel (CV) syllables that varied in their consonant place of articulation (POA) and voice onset time (VOT). Initial augmentation was maximal over several centimeters of PLST, lasted about 400 ms, and was often followed by suppression and a local outward expansion of activation. Maximal gamma power overlapped either the Nα or Pß deflections of the average evoked potential (AEP). Correlations were observed between the relative magnitudes of gamma band responses elicited by unvoiced stop CV syllables (/pa/, /ka/, /ta/) and their corresponding voiced stop CV syllables (/ba/, /ga/, /da/), as well as by the VOT of the stimuli. VOT was also represented in the temporal patterns of the AEP. These findings, obtained in the passive awake state, indicate that PLST discriminates acoustic features associated with POA and VOT and serve as a benchmark upon which task-related speech activity can be compared.

Representation of temporal sound features in the human auditory cortex.

Temporal information in acoustic signals is important for the perception of environmental sounds, including speech. This review focuses on several aspects of temporal processing within human auditory cortex and its relevance for the processing of speech sounds. Periodic non-speech sounds, such as trains of acoustic clicks and bursts of amplitude-modulated noise or tones, can elicit different percepts depending on the pulse repetition rate or modulation frequency. Such sounds provide convenient methodological tools to study representation of timing information in the auditory system. At low repetition rates of up to 8-10 Hz, each individual stimulus (a single click or a sinusoidal amplitude modulation cycle) within the sequence is perceived as a separate event. As repetition rates increase up to and above approximately 40 Hz, these events blend together, giving rise first to the percept of flutter and then to pitch. The extent to which neural responses of human auditory cortex encode temporal features of acoustic stimuli is discussed within the context of these perceptual classes of periodic stimuli and their relationship to speech sounds. Evidence for neural coding of temporal information at the level of the core auditory cortex in humans suggests possible physiological counterparts to perceptual categorical boundaries for periodic acoustic stimuli. Temporal coding is less evident in auditory cortical fields beyond the core. Finally, data suggest hemispheric asymmetry in temporal cortical processing.

Temporal envelope of time-compressed speech represented in the human auditory cortex.

Speech comprehension relies on temporal cues contained in the speech envelope, and the auditory cortex has been implicated as playing a critical role in encoding this temporal information. We investigated auditory cortical responses to speech stimuli in subjects undergoing invasive electrophysiological monitoring for pharmacologically refractory epilepsy. Recordings were made from multicontact electrodes implanted in Heschl's gyrus (HG). Speech sentences, time compressed from 0.75 to 0.20 of natural speaking rate, elicited average evoked potentials (AEPs) and increases in event-related band power (ERBP) of cortical high-frequency (70-250 Hz) activity. Cortex of posteromedial HG, the presumed core of human auditory cortex, represented the envelope of speech stimuli in the AEP and ERBP. Envelope following in ERBP, but not in AEP, was evident in both language-dominant and -nondominant hemispheres for relatively high degrees of compression where speech was not comprehensible. Compared to posteromedial HG, responses from anterolateral HG-an auditory belt field-exhibited longer latencies, lower amplitudes, and little or no time locking to the speech envelope. The ability of the core auditory cortex to follow the temporal speech envelope over a wide range of speaking rates leads us to conclude that such capacity in itself is not a limiting factor for speech comprehension.

Coding of repetitive transients by auditory cortex on Heschl's gyrus.

The capacity of auditory cortex on Heschl's gyrus (HG) to encode repetitive transients was studied in human patients undergoing surgical evaluation for medically intractable epilepsy. Multicontact depth electrodes were chronically implanted in gray matter of HG. Bilaterally presented stimuli were click trains varying in rate from 4 to 200 Hz. Averaged evoked potentials (AEPs) and event-related band power (ERBP), computed from responses at each of 14 recording sites, identified two auditory fields. A core field, which occupies posteromedial HG, was characterized by a robust polyphasic AEP on which could be superimposed a frequency following response (FFR). The FFR was prominent at click rates below approximately 50 Hz, decreased rapidly as click rate was increased, but could reliably be detected at click rates as high as 200 Hz. These data are strikingly similar to those obtained by others in the monkey under essentially the same stimulus conditions, indicating that mechanisms underlying temporal processing in the auditory core may be highly conserved across primate species. ERBP, which reflects increases or decreases of both phase-locked and non-phase-locked power within given frequency bands, showed stimulus-related increases in gamma band frequencies as high as 250 Hz. The AEPs recorded in a belt field anterolateral to the core were typically of low amplitude, showing little or no evidence of short-latency waves or an FFR, even at the lowest click rates used. The non-phase-locked component of the response extracted from the ERBP showed a robust, long-latency response occurring here in response to the highest click rates in the series.

Functional localization of auditory cortical fields of human: click-train stimulation.

Averaged auditory evoked potentials (AEPs) to bilaterally presented 100 Hz click trains were recorded from multiple sites simultaneously within Heschl's gyrus (HG) and on the posterolateral surface of the superior temporal gyrus (STG) in epilepsy-surgery patients. Three auditory fields were identified based on AEP waveforms and their distribution. Primary (core) auditory cortex was localized to posteromedial HG. Here the AEP was characterized by a robust polyphasic low-frequency field potential having a short onset latency and on which was superimposed a smaller frequency-following response to the click train. Core AEPs exhibited the lowest response threshold and highest response amplitude at one HG site with threshold rising and amplitude declining systematically on either side of it. The AEPs recorded anterolateral to the core, if present, were typically of low amplitude, with little or no evidence of short-latency waves or the frequency-following response that characterized core AEPs. We suggest that this area is part of a lateral auditory belt system. Robust AEPs, with waveforms demonstrably different from those of the core or lateral belt, were localized to the posterolateral surface of the STG and conform to previously described field PLST.

Functional connections within the human inferior frontal gyrus.

The highly convoluted and cytoarchitectonically diverse inferior frontal gyrus (IFG) of humans is known to be critically involved in a wide range of complex operations including speech and language processing. The neural circuitry that underlies these operations is not fully understood. We hypothesized that this neural circuitry includes functional connections within and between the three major IFG subgyri: the pars orbitalis, pars triangularis, and pars opercularis. To test this hypothesis we employed electrical stimulation tract-tracing techniques in 10 human patients undergoing surgical treatment for intractable epilepsy. The approach involved delivering repeated bipolar electrical stimuli to one site on the IFG while recording the electrical response evoked by that stimulus from a 64-contact grid overlying more distant IFG sites. In all subjects, stimulation of a site on one subgyrus evoked polyphasic potentials at distant sites, either on the same subgyrus or on an adjacent subgyrus. This provided prima facie evidence for a functional connection between the site of stimulation and the sites of the evoked response. The averaged evoked potentials tended to aggregate as response fields. The spatial spread of a response field indicated a divergent projection from the site of stimulation. When two or more sites were stimulated, the resulting evoked potentials exhibited different waveforms while the respective response fields could overlap substantially, suggesting that input from multiple sites converged but by engaging different neural circuits. The earliest deflection in the evoked potential ranged from 2 to 10 msec. No differences were noted between language-dominant and language-nondominant hemispheres.

Functional connections between auditory cortical fields in humans revealed by Granger causality analysis of intra-cranial evoked potentials to sounds: comparison of two methods.

Knowledge of neural interactions amongst cortical sites is important for understanding higher brain function. We studied such interactions using Granger causality (GC) to analyze auditory event-related potentials (ERPs) recorded directly and simultaneously from two physiologically identified and functionally interconnected auditory areas of cerebral cortex in human neurosurgical patients. Two methods of GC analysis were used and the results compared. Both approaches involved adaptive autoregressive modeling but differed from each other in other ways. Results obtained by using the two methods also differed. Fewer false-positive results were obtained using the method that suppressed the ERP non-stationarity and that expressed the GC as the sum of model coefficients, which suggests that this is the more appropriate approach for analyzing ERPs recorded directly from the human cortex.

Hearing suppression induced by electrical stimulation of human auditory cortex.

In the course of performing electrical stimulation functional mapping (ESFM) in neurosurgery patients, we identified three subjects who experienced hearing suppression during stimulation of sites within the superior temporal gyrus (STG). One of these patients had long standing tinnitus that affected both ears. In all subjects, auditory event related potentials (ERPs) were recorded from chronically implanted intracranial electrodes and the results were used to localize auditory cortical fields within the STG. Hearing suppression sites were identified within anterior lateral Heschl's gyrus (HG) and posterior lateral STG, in what may be auditory belt and parabelt fields. Cortical stimulation suppressed hearing in both ears, which persisted beyond the period of electrical stimulation. Subjects experienced other stimulation-evoked perceptions at some of these same sites, including symptoms of vestibular activation and alteration of audio-visual speech processing. In contrast, stimulation of presumed core auditory cortex within posterior medial HG evoked sound perceptions, or in one case an increase in tinnitus intensity, that affected the contralateral ear and did not persist beyond the period of stimulation. The current results confirm a rarely reported experimental observation, and correlate the cortical sites associated with hearing suppression with physiologically identified auditory cortical fields.

Direct recordings from the auditory cortex in a cochlear implant user.

Electrical stimulation of the auditory nerve with a cochlear implant (CI) is the method of choice for treatment of severe-to-profound hearing loss. Understanding how the human auditory cortex responds to CI stimulation is important for advances in stimulation paradigms and rehabilitation strategies. In this study, auditory cortical responses to CI stimulation were recorded intracranially in a neurosurgical patient to examine directly the functional organization of the auditory cortex and compare the findings with those obtained in normal-hearing subjects. The subject was a bilateral CI user with a 20-year history of deafness and refractory epilepsy. As part of the epilepsy treatment, a subdural grid electrode was implanted over the left temporal lobe. Pure tones, click trains, sinusoidal amplitude-modulated noise, and speech were presented via the auxiliary input of the right CI speech processor. Additional experiments were conducted with bilateral CI stimulation. Auditory event-related changes in cortical activity, characterized by the averaged evoked potential and event-related band power, were localized to posterolateral superior temporal gyrus. Responses were stable across recording sessions and were abolished under general anesthesia. Response latency decreased and magnitude increased with increasing stimulus level. More apical intracochlear stimulation yielded the largest responses. Cortical evoked potentials were phase-locked to the temporal modulations of periodic stimuli and speech utterances. Bilateral electrical stimulation resulted in minimal artifact contamination. This study demonstrates the feasibility of intracranial electrophysiological recordings of responses to CI stimulation in a human subject, shows that cortical response properties may be similar to those obtained in normal-hearing individuals, and provides a basis for future comparisons with extracranial recordings.

Direct recordings of pitch responses from human auditory cortex.

Pitch is a fundamental percept with a complex relationship to the associated sound structure. Pitch perception requires brain representation of both the structure of the stimulus and the pitch that is perceived. We describe direct recordings of local field potentials from human auditory cortex made while subjects perceived the transition between noise and a noise with a regular repetitive structure in the time domain at the millisecond level called regular-interval noise (RIN). RIN is perceived to have a pitch when the rate is above the lower limit of pitch, at approximately 30 Hz. Sustained time-locked responses are observed to be related to the temporal regularity of the stimulus, commonly emphasized as a relevant stimulus feature in models of pitch perception (e.g., [1]). Sustained oscillatory responses are also demonstrated in the high gamma range (80-120 Hz). The regularity responses occur irrespective of whether the response is associated with pitch perception. In contrast, the oscillatory responses only occur for pitch. Both responses occur in primary auditory cortex and adjacent nonprimary areas. The research suggests that two types of pitch-related activity occur in humans in early auditory cortex: time-locked neural correlates of stimulus regularity and an oscillatory response related to the pitch percept.

Directional sensitivity of neurons in the primary auditory (AI) cortex: effects of sound-source intensity level.

Transient sounds were delivered from different directions in virtual acoustic space while recording from single neurons in primary auditory cortex (AI) of cats under general anesthesia. The intensity level of the sound source was varied parametrically to determine the operating characteristics of the spatial receptive field. The spatial receptive field was constructed from the onset latency of the response to a sound at each sampled direction. Spatial gradients of response latency composing a receptive field are due partially to a systematic co-dependence on sound-source direction and intensity level. Typically, at any given intensity level, the distribution of response latency within the receptive field was unimodal with a range of approximately 3-4 ms, although for some cells and some levels, the spread could be as much as 20 or as little as 2 ms. Response latency, averaged across directions, differed among neurons for the same intensity level, and also differed among intensity levels for the same neuron. Generally, increases in intensity level resulted in decreases in the mean and variance, which follows an inverse Gaussian distribution. Receptive field models, based on response latency, are developed using multiple parameters (azimuth, elevation, intensity), validated with Monte Carlo simulation, and their spatial filtering described using spherical harmonic analysis. Observations from an ensemble of modeled receptive fields are obtained by linking the inverse Gaussian density to the probabilistic inverse problem of estimating sound-source direction and intensity. Upper bounds on acuity is derived from the ensemble using Fisher information, and the predicted patterns of estimation errors are related to psychophysical performance.

Functional connections between auditory cortex on Heschl's gyrus and on the lateral superior temporal gyrus in humans.

Functional connections between auditory fields on Heschl's gyrus (HG) and the acoustically responsive posterior lateral superior temporal gyrus (field PLST) were studied using electrical stimulation and recording methods in patients undergoing diagnosis and treatment of intractable epilepsy. Averaged auditory (click-train) evoked potentials were recorded from multicontact subdural recording arrays chronically implanted over the lateral surface of the superior temporal gyrus (STG) and from modified depth electrodes inserted into HG. Biphasic electrical pulses (bipolar, constant current, 0.2 ms) were delivered to HG sites while recording from the electrode array over acoustically responsive STG cortex. Stimulation of sites along the mediolateral extent of HG resulted in complex waveforms distributed over posterolateral STG. These areas overlapped each other and field PLST. For any given HG stimulus site, the morphology of the electrically evoked waveform varied across the STG map. A characteristic waveform was recorded at the site of maximal amplitude of response to stimulation of mesial HG [presumed primary auditory field (AI)]. Latency measurements suggest that the earliest evoked wave resulted from activation of connections within the cortex. Waveforms changed with changes in rate of electrical HG stimulation or with shifts in the HG stimulus site. Data suggest widespread convergence and divergence of input from HG to posterior STG. Evidence is presented for a reciprocal functional projection, from posterolateral STG to HG. Results indicate that in humans there is a processing stream from AI on mesial HG to an associational auditory field (PLST) on the lateral surface of the superior temporal gyrus.

A functional connection between inferior frontal gyrus and orofacial motor cortex in human.

The inferior frontal gyrus (IFG) of humans is known to play a critical role in speech production. The IFG is a highly convoluted and cytoarchitectonically diverse structure, classically forming 3 subgyri. It is reasonable to speculate that during speaking the IFG, or some portion of it, influences by corticocortical connections the orofacial representational area of primary motor cortex. To test the hypothesis that such corticocortical connections exist, electrical-stimulation tract tracing experiments were performed intraoperatively on 14 human subjects undergoing surgical treatment of medically intractable epilepsy. Bipolar electrical stimulation was applied to sites on the IFG, while the resulting evoked potentials were recorded from orofacial motor cortex, using a multichannel recording array. Stimulation of the IFG evoked polyphasic waveforms on motor cortex of both language-dominant and -nondominant hemispheres. The evoked waveforms had consistent features across subjects. The responses were seen in discrete regions on precentral cortex. Stimulation of motor cortex also evoked responses on portions of IFG. The data provide evidence for a functional connection between the human IFG and orofacial motor cortex.